Signalling Explained

We study the proteins that control communication within and between cells. They make up the signaling pathways that regulate how cells develop and respond to their environment, and are critical for ensuring the lifelong health and well being of an individual.

A common theme in all pathways is that key information is carried into the cell by molecules called lipids, which interact with various enzymes, each regulating different pathways. A major focus of our research is the activity of the PI3Kinase enzymes, critical for a number of cellular functions, including movement, growth and survival. We have developed groundbreaking technology allowing us to observe the abundance and type of lipid activated in response to external stimuli, providing a valuable tool underpinning our research. Sensing and interpreting external stimuli involves several cross-talking signalling pathways. Using state-of-the-art technologies, mathematical and computational methods and laboratory-based research we take a ‘Systems Biology’ approach to providing a comprehensive view of how genes and proteins interact.

We focus on the pathways responsible for three main areas:

Fighting Infection

Neutrophils are white blood cells that provide a rapid response to infection. Present in the blood, they recognise signals emitted from the site of infection, travel to that area and destroy the pathogen; firstly engulfing it, then releasing toxic chemicals to digest it. Elderly people have reduced ability to fight infection, partly due to a decline in neutrophil migration to sites of infection, and activation of neutrophils at inappropriate locations that damages otherwise healthy cells, resulting in disease.

We will determine the role of PI3K and other enzymes in (i) how neutrophils are attracted to the site of infection and how that declines with age, and (ii) the mechanisms that generate toxic chemicals and how production is restricted to sites of inflammation, protecting healthy cells.

Nutrient Availability

For cells to grow there must be both available nutrients and positive signals from proteins responding to environmental stimuli. This multilevel control is integrated by a single
protein, mTOR, acting as a quality control step; in favourable conditions the cells grow, if not, growth is restricted and survival pathways are activated. mTOR controls the
autophagy pathway, which during starvation periods stimulates the breakdown of cellular components allowing the cell to recycle nutrients.

Our research aims to uncover the mechanism by which PI3K influences mTOR activity, allowing it to recognize nutrient availability and control autophagy. Suppression of mTOR activity can result in increased lifespan through an unknown mechanism and we will attempt to reveal this.

Survival

We will continue to define the mechanisms that contribute to lifespan by studying a number of pathways, including how neurons survive following damage, the pathways activated to protect the cell against the presence of toxic chemicals and the pathways triggered in response to
environmental stress.